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https://www.readbyqxmd.com/read/28934472/controlled-re-activation-of-epigenetically-silenced-tet-promoter-driven-transgene-expression-by-targeted-demethylation
#1
Natascha Gödecke, Lisha Zha, Shawal Spencer, Sara Behme, Pamela Riemer, Michael Rehli, Hansjörg Hauser, Dagmar Wirth
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934386/expression-of-the-neuropathy-associated-mtmr2-gene-rescues-mtm1-associated-myopathy
#2
Matthieu A Raess, Belinda S Cowling, Dimitri L Bertazzi, Christine Kretz, Bruno Rinaldi, Jean-Marie Xuereb, Pascal Kessler, Norma B Romero, Bernard Payrastre, Sylvie Friant, Jocelyn Laporte
Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933500/significant-improvement-of-near-uv-electroluminescence-from-zno-quantum-dot-leds-via-coupling-with-carbon-nanodot-surface-plasmons
#3
Cen Zhang, Feifei Zhu, Haiyang Xu, Weizhen Liu, Liu Yang, Zhongqiang Wang, Jiangang Ma, Zhenhui Kang, Yichun Liu
Short-wavelength LEDs, a hot research topic in modern optoelectronics, have attracted tremendous attention in recent years because of their great application potential in both civil and military domains. Compared to conventional metallic surface-plasmons (SPs), carbon nanodot (CD) SPs with less optical loss and low cost, broader SP resonant frequency and good biocompatibility are expected to provide more prominent luminescence enhancement for light emitters. Herein, SP-enhanced near-UV emission quantum dot LEDs (Q-LED) were fabricated via introducing CDs into p-GaN/Al2O3/ZnO Q-LEDs by optimizing the molar ratio of ZnO quantum dots to CDs and a significant enhancement (∼20-fold) of the near-UV electroluminescence (EL) intensity from the ZnO-based Q-LEDs was achieved...
September 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28932660/atomic-scale-study-of-cation-ordering-in-potassium-tungsten-bronze-nanosheets
#4
Luying Li, Fan Jiang, Fanfan Tu, Shuangfeng Jia, Yihua Gao, Jianbo Wang
It has long been accepted that the formation of superlattices in hexagonal-based potassium tungsten bronzes is attributed to K vacancies only, together with small displacements of W cations. Here, the superlattices within potassium tungsten bronze nanosheets both structurally and spectroscopically at atomic resolution using comprehensive transmission electron microscopy techniques are studied. The multidimensional chemical analyses are realized by energy-dispersive X-ray spectroscopy, electron energy-loss spectroscopy, and X-ray photoelectron spectroscopy, the atomic-scale structures are characterized using aberration-corrected scanning transmission electron microscopy with high-angle annular-dark-field detector...
September 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28931603/the-pyhin-protein-p205-regulates-the-inflammasome-by-controlling-asc-expression
#5
Sreya Ghosh, Christina Wallerath, Sergio Covarrubias, Veit Hornung, Susan Carpenter, Katherine A Fitzgerald
Members of the IFN-inducible PYHIN protein family, such as absent in melanoma-2 and IFN-γ-inducible protein (IFI)16, bind dsDNA and form caspase-1-activating inflammasomes that are important in immunity to cytosolic bacteria, DNA viruses, or HIV. IFI16 has also been shown to regulate transcription of type I IFNs during HSV infection. The role of other members of the PYHIN protein family in the regulation of immune responses is much less clear. In this study, we identified an immune-regulatory function for a member of the murine PYHIN protein family, p205 (also called Ifi205)...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28928828/screening-of-candidate-key-genes-associated-with-human-osteosarcoma-using-bioinformatics-analysis
#6
Kefeng Zhang, Jianwen Gao, Yong Ni
The aim of the present study was to identify the key genes associated with osteosarcoma (OS) using a bioinformatics approach. Microarray data (GSE36004) was downloaded from the Gene Expression Omnibus database, including 19 OS cell lines and 6 normal controls. Differentially expressed genes (DEGs) in the OS cell lines were identified using the Limma package, and differentially methylated regions were screened with methyAnalysis in R. Copy number analysis was performed and genes with copy number gains/losses were further screened using DNAcopy and cghMCR packages...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928218/the-serine-protease-homolog-clipa14-modulates-the-intensity-of-the-immune-response-in-the-mosquito-anopheles-gambiae
#7
Johnny Nakhleh, George K Christophides, Mike A Osta
CLIP domain serine protease homologues (cSPHs) are positive and negative regulators of Anopheles gambiae immune responses mediated by the complement-like protein TEP1 against Plasmodium malaria parasites and other microbial infections. We have previously reported that the SPH CLIPA2 is a negative regulator of the TEP1-mediated response by showing that CLIPA2 knockdown (kd) enhances mosquito resistance to infections with fungi, bacteria and Plasmodium parasites. Here, we identify another SPH, CLIPA14, as a novel regulator of mosquito immunity...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928215/influenza-virus-hemagglutinin-stalk-specific-antibodies-in-human-serum-are-a-surrogate-marker-for-in-vivo-protection-in-a-serum-transfer-mouse-challenge-model
#8
Henning Jacobsen, Madhusudan Rajendran, Angela Choi, Haakon Sjursen, Karl A Brokstad, Rebecca J Cox, Peter Palese, Florian Krammer, Raffael Nachbagauer
The immunogenicity of current influenza virus vaccines is assessed by measuring an increase of influenza virus-specific antibodies in a hemagglutination inhibition assay. This method exclusively measures antibodies against the hemagglutinin head domain. While this domain is immunodominant, it has been shown that hemagglutination inhibition titers do not always accurately predict protection from disease. In addition, several novel influenza virus vaccines that are currently under development do not target the hemagglutinin head domain, but rather more conserved sites, including the hemagglutinin stalk...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28928192/a-pragmatic-group-sequential-placebo-controlled-randomised-trial-to-determine-the-effectiveness-of-glyceryl-trinitrate-for-retained-placenta-got-it-a-study-protocol
#9
Fiona C Denison, John Norrie, Julia Lawton, Jane E Norman, Graham Scotland, Gladys C McPherson, Alison McDonald, Mark Forrest, Jemma Hudson, Jane Brewin, Mathilde Peace, Cynthia Clarkson, Sheonagh Brook-Smith, Susan Morrow, Nina Hallowell, Laura Hodges, Kathryn F Carruthers
INTRODUCTION: A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). METHODS AND ANALYSIS: The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta...
September 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28928136/endothelial-epas1-deficiency-is-sufficient-to-promote-parietal-epithelial-cell-activation-and-fsgs-in-experimental-hypertension
#10
Yosu Luque, Olivia Lenoir, Philippe Bonnin, Lise Hardy, Anna Chipont, Sandrine Placier, Sophie Vandermeersch, Yi-Chun Xu-Dubois, Blaise Robin, Hélène Lazareth, Michèle Souyri, Léa Guyonnet, Véronique Baudrie, Eric Camerer, Eric Rondeau, Laurent Mesnard, Pierre-Louis Tharaux
FSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive...
September 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28927930/biodegradable-and-adjustable-sol-gel-glass-based-hybrid-scaffolds-from-multi-armed-oligomeric-building-blocks
#11
Christian Kascholke, Stephan Hendrikx, Tobias Flath, Dzmitry Kuzmenka, Hans-Martin Dörfler, Dirk Schumann, Mathias Gressenbuch, F Peter Schulze, Michaela Schulz-Siegmund, Michael C Hacker
Biodegradability is a crucial characteristic to improve the clinical potential of sol-gel-derived glass materials. To this end, a set of degradable organic/inorganic class II hybrids from a tetraethoxysilane(TEOS)-derived silica sol and oligovalent cross-linker oligomers containing oligo(D,L-lactide) domains was developed and characterized. A series of 18 oligomers (Mn: 1100-3200 Da) with different degrees of ethoxylation and varying length of oligoester units was established and chemical composition was determined...
September 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28927887/epidermal-overexpression-of-xenobiotic-receptor-pxr-impairs-the-epidermal-barrier-and-triggers-th2-immune-response
#12
Andreas Elentner, Matthias Schmuth, Nikolaos Yannoutsos, Thomas O Eichmann, Robert Gruber, Franz Pw Radner, Martin Hermann, Barbara Del Frari, Sandrine Dubrac
The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain under-investigated. Many of these toxins bind and activate the pregnane x receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model which overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28927429/the-impact-of-lipoprotein-lipase-deficiency-on-health-related-quality-of-life-a-detailed-structured-qualitative-study
#13
Sasi Neelamekam, See Kwok, Rachel Malone, Anthony S Wierzbicki, Handrean Soran
BACKGROUND: Lipoprotein lipase deficiency (LPLD) is an autosomal recessive inherited disorder caused by loss-of-function mutations in genes involved in the lipoprotein lipase pathway. It is characterised by chylomicronaemia, severe hypertriglyceridaemia and an increased risk of recurrent pancreatitis that often requires hospitalisation. This research aimed to improve our understanding of the debilitating impact that LPLD has on the daily lives of patients and their families. METHODS: The research comprised a 2-h interview with the patient and, where possible, a 1-h interview with a family member; a 1-week pre- and post-interview task (written and/or video diary); and a 30-45-min follow-up telephone interview...
September 19, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28926646/vascular-hypoperfusion-in-acute-optic-neuritis-is-a-potentially-new-neurovascular-model-for-demyelinating-diseases
#14
Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, Fung-Rong Hu
PURPOSE: Optic neuritis is highly correlated with multiple sclerosis and is a major cause of acute visual loss and long-term neuronal degeneration. Primary cerebral hypoperfusion has been reported in brain demyelinating diseases. This study investigated whether peripapillary perfusion is changed in patients with acute optic neuritis (AON). METHODS: This three-year cohort study was conducted from September 1 2012, to August 31, 2015. Two hundred and forty-one patients with non-glaucomatous acute optic neuropathy were screened, and 42 non-highly myopic patients who had suffered their first episode of unilaterally idiopathic AON were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28926230/formation-and-characterization-of-hydrogen-boride-sheets-derived-from-mgb2-by-cation-exchange
#15
Hiroaki Nishino, Takeshi Fujita, Nguyen Thanh Cuong, Satoshi Tominaka, Masahiro Miyauchi, Soshi Iimura, Akihiko Hirata, Naoto Umezawa, Susumu Okada, Eiji Nishibori, Asahi Fujino, Tomohiro Fujimori, Shin-Ichi Ito, Junji Nakamura, Hideo Hosono, Takahiro Kondo
Two-dimensional (2D) materials are promising for applications in a wide range of fields because of their unique properties. Hydrogen boride sheets, a new 2D material recently predicted from theory, exhibit intriguing electronic and mechanical properties as well as hydrogen storage capacity. Here, we report the experimental realization of 2D hydrogen boride sheets with an empirical formula of H1B1, produced by exfoliation and complete ion-exchange between protons and magnesium cations in magnesium diboride (MgB2) with an average yield of 42...
September 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28922944/revised-inverse-problem-algorithm-based-prediction-of-coronary-artery-stenosis-readings-from-the-clinical-data-of-patients-with-coronary-heart-diseases
#16
Lung-Fa Pan, Shao-Wen Chiu, Min-Feng Xiao, Chia-Hui Chen, Lung-Kwang Pan
AIM: Coronary artery stenosis readings were predicted in this study on the basis of clinical data for patients with coronary heart diseases using the inverse problem algorithm. METHOD: Five factors, including age, BSA (body surface area), MAP (mean artery pressure), sugar AC (ante cibum), and LDL-C (low-density Lipoprotein-Cholesterol) were incorporated into a nonlinear first-order regression fit analysis to develop a prediction equation with sixteen terms derived via a revised inverse problem algorithm implemented through the STATISTICA default regression fit...
September 18, 2017: Computer Assisted Surgery (Abingdon, England)
https://www.readbyqxmd.com/read/28922745/big-brother-uncouples-cell-proliferation-from-elongation-in-the-arabidopsis-primary-root
#17
Pietro Cattaneo, Christian S Hardtke
Plant organ size is sensitive to environmental conditions, but is also limited by hardwired genetic constraints. In Arabidopsis, a few organ size regulators have been identified. Among them, the BIG BROTHER (BB) gene has a prominent role in the determination of flower organ and leaf size. BB loss-of-function mutations result in a prolonged proliferation phase during leaf(-like) organ formation, and consequently larger leaves, petals and sepals. Whether BB has a similar role in root growth is unknown. Here we describe a novel bb allele which carries a P235L point mutation in the BB RING finger domain...
September 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28922740/a-conserved-dggk-motif-is-essential-for-the-function-of-the-pglb-oligosaccharyltransferase-from-campylobacter-jejuni
#18
Yasmin Barre, Harald Nothaft, Cody Thomas, Xin Liu, Jianjun Li, Kenneth K S Ng, Christine M Szymanski
In Campylobacter jejuni, the PglB oligosaccharyltransferase catalyzes the transfer of a heptasaccharide from a lipid donor to asparagine within the D/E-X1-N-X2-S/T sequon (X1,2 ≠ P) or releases this heptasaccharide as free oligosaccharides (fOS). Using available crystal structures and sequence alignments, we identified a DGGK motif near the active site of PglB that is conserved among all Campylobacter species. We demonstrate that amino acid substitutions in the aspartate and lysine residues result in loss of protein glycosylation in the heterologous Escherichia coli system...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28919773/sickle-cell-retinopathy-improving-care-with-a-multidisciplinary-approach
#19
REVIEW
Farid Menaa, Barkat Ali Khan, Bushra Uzair, Abder Menaa
Sickle cell retinopathy (SCR) is the most representative ophthalmologic complication of sickle cell disease (SCD), a hemoglobinopathy affecting both adults and children. SCR presents a wide spectrum of manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated at the earliest. Over the past decade, multidisciplinary research developments have focused upon systemic, genetic, and ocular risk factors of SCR, enabling the clinician to better diagnose and manage these patients...
2017: Journal of Multidisciplinary Healthcare
https://www.readbyqxmd.com/read/28919464/corticothalamic-network-dysfunction-and-alzheimer-s-disease
#20
Rohan Jagirdar, Jeannie Chin
Alzheimer's disease (AD) is a devastating neurodegenerative disease that is characterized by progressive cognitive decline and a prominent loss of hippocampal-dependent memory. Therefore, much focus has been placed on understanding the function and dysfunction of the hippocampus in AD. However, AD is also accompanied by a number of other debilitating cognitive and behavioral alterations including deficits in attention, cognitive processing, and sleep maintenance. The underlying mechanisms that give rise to impairments in such diverse behavioral domains are unknown, and identifying them would shed insight into the multifactorial nature of AD as well as reveal potential new therapeutic targets to improve overall function in AD...
September 14, 2017: Brain Research
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